Dr. Jared Gardner, along with dermatology residents and fellows, conducts a detailed review of 18 diverse dermatopathology cases, focusing heavily on neural and soft tissue tumors. The session highlights fundamental diagnostic clues for common entities such as neurofibroma (S/comma-shaped nuclei, mixoid matrix, low power pale pink color), schwannoma (Antoni A/B areas, capsulation), and granular cell tumor (granular cytoplasm, pseudo-infiltrative growth, PEH association). Emphasis is placed on distinguishing related entities, including the difference between nerve sheath mixoma and cellular neurotheoma, and the use of architecture (whirling/storiform patterns in perineuroma and DFSP). The discussion also covers malignant tumors like high-mitotic rate Merkel cell carcinoma and the diagnostic implications of translocation sarcomas (DFSP), along with specialized histiocytic processes such as Rosai-Dorfman disease and Juvenile Xanthogranuloma. Key diagnostic takeaways involve recognizing subtle cytologic features, identifying characteristic background stroma, and selecting appropriate immunohistochemical stains (e.g., CK20, TTF1, S100) to confirm diagnoses or rule out serious mimics.
Dermatopathology Case Review: Neural and Soft Tissue Tumors
0:18 Case 1: Neurofibroma. Characterized by deep dermal, pale pink nodules composed of gently wavy, S or comma-shaped schwann cells (0:40). Other key features include loose, mixoid ground substance (02:56) creating a pale pink color relative to background collagen (often called "bubble gum pink"), and scattered mast cells (02:13). The tumor exhibits infiltration and entrapment of fat and adnexal structures (05:08), a feature sometimes seen in diffuse neurofibroma.
6:03 Case 2: Merkel Cell Carcinoma (MCC). A highly aggressive, small, deep blue cell tumor with very little cytoplasm and smudgy nuclear chromatin (06:37). It is distinguished by an extremely high mitotic rate (08:30) (often >100 per mm²). MCC is differentiated from small cell lung carcinoma using CK20 (+) (often peri-nuclear dot pattern) and TTF1 (-) (11:17). The tumor frequently shows nesting and clumping (09:56), indicating its epithelial/carcinoma nature.
12:48 Case 3: Granular Cell Tumor (GCT). Not well-circumscribed, showing a characteristic "trickling" or "oozing" growth pattern (14:28) between collagen bundles without causing a reactive stromal change (14:53). The cytoplasm is grainy (granular) due to phagolysosomes (15:33). Diagnosis is supported by S-100 and CD68 positivity. Intraneural involvement is common (~90%) (17:30) and is expected, not worrisome.
18:01 Case 4: Perineuroma. Features plump spindle cells in a dense collagen background, exhibiting a distinctive swirling or whirling architecture (19:27). It is S-100 negative and characteristically EMA positive (21:19). The Sclerosing type is often found on acral surfaces (20:44).
25:46 Case 6: Dermatofibrosarcoma Protuberance (DFSP). Classically presents with infiltration of subcutaneous fat, creating a "Swiss cheese pattern" (25:53). Cytology is bland (28:24). While the cells can mimic neural tumors, DFSP is S-100 negative and strongly CD34 positive (27:52). The takeaway emphasizes that CD34 is sensitive but not specific, and the key architectural buzzword is the storiform pattern (30:49, shown in external slide).
31:48 Case 7: Schwannoma. Presents as a deep, sharply circumscribed and encapsulated nodule (32:03, 35:10) in the subcutis. Features cellular Antoni A areas (with palisading/Verocay-like bodies, 34:17) and hypocellular Antoni B areas. Hemorrhage and hemosiderin deposition are common (33:30).
37:04 Case 8: Merkel Cell Carcinoma (MCC) with Squamous Cell Carcinoma in situ (SCCis). An important co-occurrence. MCC forms the blue dermal nodule, while the overlying epidermis shows full thickness atypia (37:56) characteristic of Bowen's disease (SCCis). The high frequency of this co-presentation suggests a likely non-coincidental relationship or shared pathway (38:48).
41:32 Case 9: Nerve Sheath Mixoma. Defined by its architecture: multiple small mixoid nodules packed within a larger circumscribed nodule (41:42). This entity is S-100 positive, differentiating it from cellular neurotheoma (S-100 negative, 42:42).
44:47 Case 10: Angioleiomyoma. Identified as a "pink marble" (45:01) tumor containing prominent thick-walled blood vessels (45:18). It is composed of smooth muscle cells with characteristic blunt-ended, cigar-shaped nuclei (45:45). These tumors are often painful and usually located in the subcutis of the lower legs.
50:38 Case 12: Rosai-Dorfman Disease (RDD). Microscopically appears as sheets of huge, pale-pink histiocytes (51:58) intermixed with dark blue lymphocytes. The diagnostic hallmark is emperipolesis (52:34)—the presence of intact lymphocytes or other white/red blood cells sitting within the histiocytes' cytoplasm. RDD histiocytes are S-100 positive (53:14).
1:10:01 Case 21: Granular Cell Tumor (GCT) with PEH. A GCT located on the tongue (skeletal muscle background). The GCT itself is classic, but the overlying squamous epithelium shows dramatic proliferation mimicking invasive Squamous Cell Carcinoma (PEH) (1:11:16). The takeaway is crucial: when SCC is suspected in oral mucosa, check the underlying stroma for granular cells to avoid an overdiagnosis of cancer (1:11:53).
1:15:43 Case 23: Palisaded Encapsulated Neuroma (PEN). A benign neural lesion that is the likely diagnosis if a schwannoma is suspected in the dermis (1:15:57). Key features include palisading bundles separated by prominent clefting artifact (1:16:18).
1:17:24 Case 24: Juvenile Xanthogranuloma (JXG). A histiocytic lesion classically diagnosed by the presence of histiocytes, eosinophils (1:18:13), and the pathognomonic Touton Giant Cell (1:17:35)—a multinucleated cell with a ring of nuclei and foamy cytoplasm. Can occur in adults.